2022 World Conference on Lung Cancer (ePosters)-EP16.03-020. High Tumor Mutational Burden by Whole-Genome Sequencing in Resected NSCLC in Never Smokers is Associated with Worse Prognosis

EP16.03-020. High Tumor Mutational Burden by Whole-Genome Sequencing in Resected NSCLC in Never Smokers is Associated with Worse Prognosis

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A study conducted at the Institut universitaire de cardiologie et de pneumologie de Québec – Université Laval in Canada has found that a high tumor mutational burden (TMB) in never-smokers with non-small cell lung cancer (NSCLC) is associated with a worse prognosis. The researchers used whole-genome sequencing (WGS) to assess the TMB in 92 paired tumor-normal samples from never-smokers who underwent NSCLC resection. They compared the TMB derived from WGS with that obtained from in-silico reduced whole-exome sequencing (WES) and commercial next-generation sequencing (NGS) gene panels.<br /><br />The results showed that the median TMB by WGS was 1.57 mutations per megabase (mut/Mb), and a cutoff of 1.70 mut/Mb was associated with a 5-year overall survival of 58% in high-TMB patients compared to 86% in low-TMB patients. WGS revealed a higher number of mutations compared to WES. TMB scores from WGS and WES were highly correlated, while those from NGS panels showed high intra-individual fluctuations and were not reliable for TMB estimation in never-smokers.<br /><br />The study concluded that a high TMB based on a cutoff of 1.70 mut/Mb was observed in 42% of cases and was associated with worse prognosis in never-smokers with NSCLC. WES was found to be an accurate approach to estimate TMB, while targeted NGS panels lacked the depth and resolution to accurately estimate TMB in this population.<br /><br />The researchers recommend further studies to validate and confirm these findings and to explore the potential clinical utility of TMB as a prognostic biomarker in never-smokers with NSCLC. They also highlight the importance of using WGS or WES for accurate TMB estimation in this population.

Asset Subtitle

Louis-Jacques Ruel

Meta Tag

Speaker Louis-Jacques Ruel

Topic Tumour Biology and Biomarkers - Molecular Profiling and Targeted Therapies

Keywords

study

tumor mutational burden

never-smokers

non-small cell lung cancer

prognosis

whole-genome sequencing

WGS

WES

NGS panels

prognostic biomarker